Employment of adult mammalian primary cells in toxicology: in vivo and in vitro genotoxic effects of environmentally significant N-nitrosodialkylamines in cells of the liver, lung, and kidney.
This report focuses on the use of freshly isolated primary mammalian cells from different tissues and organs of the rat for the rapid and efficient analysis of toxic and genotoxic chemicals. The cells are either treated in vitro or they are isolated from treated animals. Viability by trypan blue exclusion and DNA damage as single-strand breaks are monitored in either case. Therefore, it is possible to compare in vitro and in vivo results directly. N-nitrosamines with unique organ-specific modes in carcinogenesis were studied in vitro using hepatocytes derived from three species (rat, hamster, and pig) and in rat lung and kidney cells. The sensitive detection of all carcinogenic nitrosamines was achieved, although a pattern of cell-specific activation was not observable. The new modification of the in vivo approach allowed the sensitive detection of NDMA genotoxicity in hepatic and in extrahepatic tissues. It is important to point out that the method is an efficient tool for toxicokinetic studies with genotoxic carcinogens in vivo.
Pool
B L
BL
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
Brendler
S Y
SY
Liegibel
U M
UM
Tompa
A
A
Schmezer
P
P
D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004249:DNA Damage; D005260:Female; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008647:Mesocricetus; D009152:Mutagenicity Tests / Q000379:methods*; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D009602:Nitrosamines